Autophagy-Sirt3 axis decelerates hematopoietic aging.

ABSTRACT: Autophagy suppresses mitochondrial metabolism to preserve hematopoietic stem cells (HSCs) in mice. However, the mechanism by which autophagy regulates hematopoietic aging, in particular in humans, has largely been unexplored. Here, we demonstrate that reduction of autophagy in both hematopoietic cells and their stem cells is associated with aged hematopoiesis in human population. Mechanistically, autophagy delays hematopoietic aging by activating the downstream expression of Sirt3, a key mitochondrial protein capable of rejuvenating blood. Sirt3 is the most abundant Sirtuin family member in HSC-enriched population, though it declines as the capacity for autophagy deteriorates with aging. Activation of autophagy upregulates Sirt3 in wild-type mice, whereas in autophagy-defective mice, Sirt3

SUBMITTER: Fang Y 

PROVIDER: S-EPMC7576273 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature